Showing papers by "John W. Erdman published in 2002"

Bioavailability of all-trans and cis-isomers of lycopene.

Abstract: Lycopene, the predominant carotenoid in tomatoes, is among the major carotenoids in serum and tissues of Americans. Although about 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues contain mainly cis-isomers. Several research groups have suggested that cis-isomers of lycopene are better absorbed than the all-trans form because of the shorter length of the cis-isomer, the greater solubility of cis-isomers in mixed micelles, and/or as a result of the lower tendency of cis-isomers to aggregate. Work with ferrets, a species that absorbs carotenoids intact, has demonstrated that whereas a lycopene dose, stomach, and intestinal contents contained 6-18% cis-lycopene, the mesenteric lymph secretions contained 77%-cis isomers. The ferret studies support the hypotheses that cis-isomers are substantially more bioavailable then all-trans lycopene. In vitro studies suggest that cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons. The implications of these findings are not yet clear. Rats appear to accumulate lycopene in tissues within the ranges reported for humans, suggesting that they can be used to study effects of lycopene isomers on disease processes. Investigations are underway to determine whether there are biological differences between all-trans and various cis-isomers of lycopene regarding its antioxidant properties or other biological functions.

All-trans β-Carotene Appears to Be More Bioavailable than 9-cis or 13-cis β-Carotene in Gerbils Given Single Oral Doses of Each Isomer

Abstract: Male gerbils (28 d old) were used to investigate the beta-carotene (betaC) isomer pattern in the intestine and tissues 6 h after ingestion of three betaC isomers. After a 49- to 52-d period of consuming the AIN93G diet without vitamin A (VA) or betaC, three groups (n = 7) were gavaged with crystalline all-trans (at)betaC, 9-cis (9c)betaC or 13-cis (13c)betaC solubilized in oil and a control group (n = 5) with oil alone. Total betaC per dose for gerbils in the atbetaC, 9cbetaC and 13cbetaC groups was 384 +/- 3, 391 +/- 2 and 386 +/- 2 nmol, respectively. After 6 h, gerbils were killed and serum, stomach contents, small intestinal contents (SIC), small intestinal mucosal scrapings (SIM) and liver were collected. betaC and VA in tissues were quantified using HPLC. Nonspecific isomerization of betaC occurred in the digestive tracts of gerbils administered betaC; the greatest effect was in the SIC of the 13cbetaC (50:50 cis:trans) and 9cbetaC (70:30 cis:trans) groups. Concentrations of total betaC in the SIM of gerbils administered at betaC were greater than those intubated with 9cbetaC and 13cbetaC (P < 0.05). Gerbils that received atbetaC had greater total betaC concentrations in serum (P < 0.05) and total betaC stores in liver (P < 0.01) compared with those administered 9cbetaC and 13cbetaC. Gerbils intubated with 9cbetaC had higher levels of total betaC in serum (P = 0.05) and liver (P < 0.01) compared with those intubated with 13cbetaC. Because of its preferential uptake, transport and tissue accumulation, atbetaC appears to be a more bioavailable isomer than 9cbetaC or 13cbetaC in gerbils.

Lycopene, tomato products, and prostate cancer prevention. Have we established causality?

Abstract: The relationship between tomato products and prostate cancer prevention has been the subject of increasingly intense research activity over the past decade. The hypothesis that tomato products contain phytochemicals, perhaps lycopene and others, that modify prostate carcinogenesis warrants investigation. However, scientists, regulatory agencies, marketers of products, and those defining public health policy have differing opinions regarding the strength of the data when applied to criteria for inference and causality. It is useful to briefly review these criteria and discuss the relative strengths and weaknesses of the published data in order to better define future directions for research. Accepted categories of criteria include: consistency, strength of association, biological gradient, temporality, specificity, biological mechanisms and coherence, and experimental evidence. We believe that continued support for research regarding tomato products, lycopene and other phytochemicals, and prostate cancer risk is warranted and may ultimately serve as the basis for more consistent public health recommendations for the consumer. But, what do we say to the public when the data is still inconclusive? The authors support the recommendation that a minimum of five serv- ings of fruit and vegetables should be consumed daily from a variety of sources. We believe that the hypothesized benefits of tomato products for prostate cancer prevention may be achieved with approximately five servings of tomato products per week. The consumption of lycopene supplements is not currently recommended for prostate cancer prevention or ther- apy. Future research will allow us to provide more definitive guidelines.

The Relative Vitamin A Value of 9-cis β-Carotene Is Less and That of 13-cis β-Carotene May Be Greater than the Accepted 50% That of All-trans β-Carotene in Gerbils

Abstract: The effectiveness of beta-carotene (betaC) as a vitamin A (VA) precursor may be influenced by the proportions of cis isomers of betaC consumed in the diet. Although the metabolic fates of cis isomers of betaC are poorly understood, their retinol equivalency has been assigned a value 50% that of all-trans (at) betaC. A dose-response design was used to estimate the relative VA value (VAV) of atbetaC, 9-cis (9c) betaC and 13-cis (13c) betaC in gerbils using total liver retinol as a measure of VAV. Ten groups of gerbils received a daily dose of oil with or without betaC isomer by gavage for 7 d. Nine groups (n = 5) were divided equally among the three betaC dosing treatments with each isomer provided at 141, 275 and 418 nmol/d. Total liver VA (171-259 nmol) in gerbils administered atbetaC was higher than total liver betaC (25-53 nmol). Stores of VA and betaC in livers from gerbils administered atbetaC were higher than stores of VA and betaC in livers from those given 9cbetaC or 13cbetaC. The relative VAV of cis betaC isomers was estimated by comparing slopes of dose-response lines of all three betaC isomers using atbetaC as a reference. Total liver VA and betaC increased linearly (P < 0.05) with increasing betaC intake in gerbils gavaged with all three betaC isomer oils. The relative VAV of 9cbetaC was less (38%) and 13cbetaC was more (62%) than the assigned value of 50% that of atbetaC. Thus, the proportions of cis isomers of betaC contained in a food could negatively affect the vitamin A value of the diet.

Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats

Abstract: Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processes during prostate carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in male Wistar-Unilever rats. Immunohistochemical and digital image analysis techniques were used to evaluate the proliferation index, the apoptotic index and microvessel density (MVD) in tissue representing stages of prostate carcinogenesis. The proliferation index in the normal glandular epithelium of the prostate is lower than that observed in hyperplastic foci and atypical hyperplasia (P < 0.01) and is further increased in carcinoma (P < 0.01). Apoptosis in the normal prostate epithelium or hyperplastic lesions is lower than in adenocarcinoma (P < 0.01). In parallel to proliferation index, MVD increases as prostate cancer progresses. As tumors enlarge, we observed a predictable change in biomarker expression within the tumor microenvironment. We examined prostate tumors vertical line 1 cm in diameter and biomarker expression was quantified within the peripheral (outer 1-2 mm), central (perinecrotic) and intermediate (remaining) areas of each tumor. The proliferation index is higher (P < 0.01) in the intermediate area than either in the peripheral area or central area. Similarly, the vascular density in the intermediate area is higher (P < 0.01) than either in the peripheral or central area. The apoptotic index is higher (P < 0.05) in the central perinecrotic core than that in either the intermediate or the peripheral area. In conclusion, we observe that angiogenesis, proliferation and apoptosis are linked biological processes predictably altered temporally and spatially during prostate carcinogenesis in the MNU model. These biomarker changes are similar to those reported in human prostate carcinogenesis and represent potential biomarkers for the assessment of dietary, chemopreventive and therapeutic agents.